The study, conducted in mice, appears in this week's early edition of the Proceedings of the National Academy of Sciences, and holds
promise for preventing the painful episodes and organ damage that are common complications of sickle cell disease.

According to the U-M study, increasing the expression of the proteins, TR2 and TR4, more than doubled the level of fetal hemoglobin produced in
sickle cell mice and reduced organ damage.

"The vast majority of sickle cell disease patients are diagnosed early in childhood when adult hemoglobin normally replaces fetal hemoglobin,
but the severity of the disease can differ markedly, correlating most strongly with the level of fetal hemoglobin present in red cells," says
pediatrician and lead study author Andrew D. Campbell, M.D., director of the
Pediatric Comprehensive Sickle Cell Program at the U-M Comprehensive
Cancer Center.

It's most common among those with an ancestry to Africa, South and Central America, the Caribbean islands, India, Saudi Arabia and
Mediterranean countries such as Turkey, Greece and Italy.

But a small number of sickle cell patients are born with a high enough fetal hemoglobin level to moderatecomplications.

The study team, that included experts in hematology oncology, cell and developmental biology and pathology from the U-M and the University of
Tsukuba, Japan, demonstrated a potential method for boosting the fetal hemoglobin levels by modulating TR2/TR4 expression.

It's the first time specific proteins have been targeted to prevent a disease, he says.

Anemia and red blood cell turnover all improved within the TR2/TR4 treated mice. Additional studies, including clinical trials, would be
required to determine if the method could help humans.

"Currently hydroxyurea is the only FDA approved drug known to increase the levels of fetal hemoglobin within sickle cell disease patients and a
substantial number of patients do respond to it," says Campbell, the pediatric hematology oncology specialist. "But the long term consequences for
hydroxyurea are unknown, especially in children."

Funding:
Authors work was supported by the American Heart Association, Cooley's Anemia Foundation, Robert Wood Johnson Foundation and the National
Institutes of Health's National Heart Lung and Blood Institute.